Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models

Fernando F. Corrales-Medina, Christa A. Manton, Robert Z. Orlowski, Joya Chandra

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Current relapse rates in acute myeloid leukemia (AML) highlight the need for new therapeutic strategies. Panobinostat, a novel pan-histone deacetylase inhibitor, and marizomib, a second-generation proteasome inhibitor, are emerging as valuable therapeutic options for hematological malignancies. Here we evaluated apoptotic effects of this combinatorial therapy in AML models and report earlier and higher reactive oxygen species induction and caspase-3 activation and greater caspase-8 dependence than with other combinations. In a bortezomib refractory setting, panobinostat induced high levels of DNA fragmentation, and its action was significantly augmented when combined with marizomib. These data support further study of this combination in hematological malignancies.

Original languageEnglish (US)
Pages (from-to)371-379
Number of pages9
JournalLeukemia Research
Volume39
Issue number3
DOIs
StatePublished - Mar 1 2015

Keywords

  • Acute myeloid leukemia
  • Bortezomib
  • Marizomib
  • Multiple myeloma
  • Panobinostat

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Efficacy of panobinostat and marizomib in acute myeloid leukemia and bortezomib-resistant models'. Together they form a unique fingerprint.

  • Cite this